EFFECT OF GINSENG ON CISPLATIN-INDUCED EMESIS

描述(申请人提供)：用顺铂等血液治疗药物治疗癌症会产生严重的不良反应，不仅会降低患者的生活质量，还可能导致他们拒绝接受有潜在疗效的化疗。恶心呕吐是化疗药物的一种重要不良反应，应加以控制，以减少发病率，提高化疗效果。目前可用的止吐药物可以缓解症状，特别是在联合使用时，但会导致额外的药物相关不良事件和药物-药物相互作用的可能性。顺铂诱导的胃排空延迟也可能参与恶心/呕吐的发病机制。导致胃肠道病理的种子事件可能是由肠道氧化损伤期间释放的神经递质引起的。因此，我们建议使用草本抗氧化剂西洋参来对抗氧化事件，并确定其在治疗顺铂引起的呕吐方面的潜力。我们将研究西洋参根提取物(AGRE)和西洋参浆果提取物(AGBE)及其活性成分(人参皂苷Rg1、Rb1、Re和Rd)在减少化疗引起的恶心/呕吐和改善大鼠胃排空方面的作用。老鼠对顺铂等呕吐刺激的反应是通过改变饮食习惯来实现的，表现为增加了高岭土(一种粘土)等非营养性物质的摄入量，高岭土被称为Pica。顺铂导致高岭土消耗量显著增加，该模型已被用于评估新的止吐化合物。此外，顺铂还可以延缓大鼠的胃排空。我们假设，给予AGRE、AGBE及其活性成分将有效地减少PICA并改善胃排空，同时保留顺铂的杀瘤活性。在这项拟议的研究中，我们将评估AGRE、AGBE和人参皂苷Rg1、Rb1、Re和Rd对顺铂治疗大鼠的止吐活性，并确定草药对顺铂杀瘤活性的影响。由于西洋参在其他组织中具有抗肿瘤活性和对化疗药物的抗氧化保护作用，我们预计西洋参将成为癌症化疗中一种有效的止吐药物。

DESCRIPTION (provided by applicant): Treatment of cancer with hemotherapeutic agents such as cisplatin is associated with severe adverse effects that not only worsen patients' quality of life but also could lead to their refusal of potentially curative chemotherapy. Nausea/vomiting, a significant adverse effect of chemotherapeutic drugs, should be adequately controlled to reduce morbidity and improve effectiveness of chemotherapy. The currently available anti-emetic drugs relieve the symptoms especially when used in combinations, but lead to the possibility of additional drug-related adverse events and drug-drug interactions. Cisplatin-induced delayed gastric emptying could also contribute to the pathogenesis of nausea/vomiting. The seminal event that causes the gastrointestinal pathology is likely caused by neurotransmitters released during oxidant injury to the gut. We therefore propose to use an herbal anti-oxidant, American ginseng, to antagonize the oxidant events and to determine it's potential in treating cisplatin-induced emesis. We will investigate the role of American ginseng root extract (AGRE) and American ginseng berry extract (AGBE), and their active constituents (ginsenosides Rg1, Rb1, Re, and Rd ), in reducing chemotherapy-induced nausea/vomiting and in improving gastric emptying in a rat model. Rats react to emetic stimuli, like cisplatin, by altered feeding habits, manifested as increased consumption of non-nutritive substances like kaolin (a type of clay), known as pica. Cisplatin induces a significant increase in kaolin consumption, and this rat model has been utilized to evaluate novel anti-emetic compounds. In addition, cisplatin also delays gastric emptying in rats. We hypothesize that administration of AGRE, AGBE and their active constituents will effectively reduce pica and improve gastric emptying, while preserving the tumoricidal activity of cisplatin. In the proposed study, we will evaluate anti-emetic activities of AGRE, AGBE and ginsenosides Rg1, Rb1, Re, and Rd in rats treated with cisplatin, and determine herbal effects on the tumoricidal activity of cisplatin. Due to the fact that ginseng has shown tumoricidal properties and antioxidant protection from chemotherapeutic agents in other tissues, we expect that American ginseng will be an efficacious anti-emetic treatment in cancer chemotherapy.